田清菁,苏钰清,宋艳志,全晶晶,李博群,邓意辉
TIAN Qingjing,SU Yuqing,SONG Yanzhi,QUAN Jingjing,LI Boqun,DENG Yihui

• 1:沈阳药科大学药学院

摘要(Abstract)：

目的比较纯化和市售聚乙二醇1000维生素E琥珀酸酯(d-α-tocopherol polyethylene glycol1000 succinate,TPGS)的纯度,并对不同来源的TPGS大鼠静脉注射的药动学行为进行考察。方法采用高效液相色谱-蒸发光散射检测器(HPLC-ELSD)法,对不同来源TPGS(分别为纯化、德国BASF公司和美国Sigma公司)中主要杂质聚乙二醇1000(PEG1000)和聚乙二醇1000维生素E琥珀酸双酯(di-d-α-tocopherol polyethylene glycol 1000 succinate,di-TPGS)的含量进行测定,计算TPGS纯度。以DiR为模型药物,采用荧光分析法考察不同来源TPGS的药动学行为。结果与市售TPGS相比,纯化TPGS(TPGS-Purified)、BASF来源的TPGS(TPGS-BASF)和Sigma来源的TPGS(TPGS-Sigma)纯度分别为100.0%、86.70%和90.98%。以聚山梨酯80(Tween 80)作为参照,TPGS-Purified/DiR、TPGS-BASF/DiR和TPGS-Sigma/DiR的AUC(0-24 h)和MRT(0-24 h)分别为Tween80/DiR的2.75、2.53、2.72倍和1.77、1.68、1.84倍。各TPGS/DiR组中AUC(0-24 h)和MRT(0-24 h)均无显著性差异。结论 TPGS-Purified纯度接近于100%,以其制备的胶束循环时间较长,为高纯度TPGS在静脉注射中的应用提供了一定指导。
Objective To compare the purity of purified TPGS( TPGS-purified) and commercial TPGS( TPGS-BASF,TPGS-Sigma),and to investigate the pharmacokinetic profiles of TPGS micelles in normal Wistar rat. Methods A HPLC-ELSD method w as established for the determination of PEG1000 and di-TPGS in TPGS to compare the purity of TPGS from different resource. Pharmacokinetics behavior of TPGS micelles in rats w as investigated using DiR as the tracer. Results The purity of TPGS-purified,TPGS-BASF and TPGS-Sigma w ere 100%,86. 70% and 90. 08%,respectively. Compared to the Tw een 80/DiR,the AUC( 0-24 h)of TPGS-purified/DiR,TPGS-BASF/DiR and TPGS-Sigma/DiR w ere observed to be 2. 75,2. 53 and 2. 72-fold higher,respectively,and the MRT( 0-24 h)of TPGS-purified/DiR,TPGS-BASF/DiR and TPGS-Sigma/DiR w ere 1. 77,1. 68 and 1. 84-fold increased,respectively. Conclusions The purity of purified TPGS w as nearly 100%,and the results of pharmacokinetic study proved the long circulation time of TPGS micells,w hich providing a reference for the application of TPGS w ith high purity in intravenous injections.

关键词(KeyWords)： 聚乙二醇1000维生素E琥珀酸酯;纯度分析;DiR;药动学;静脉注射
d-α-tocopherol polyethylene glycol 1000 succinate;purity determination;DiR;pharmacokinetics;intravenous injection

Abstract:

Keywords:

基金项目(Foundation): 国家自然科学基金资助项目(81373334)

作者(Author): 田清菁,苏钰清,宋艳志,全晶晶,李博群,邓意辉
TIAN Qingjing,SU Yuqing,SONG Yanzhi,QUAN Jingjing,LI Boqun,DENG Yihui

DOI: 10.14066/j.cnki.cn21-1349/r.2018.01.003

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